This program-project proposal represents a collaborative and cooperative effort by a group of 21 investigators with wide ranging research interests in cell membranes. We are requesting core support for eight faculty members from the Department of Microbiology, eight from the Department of Biochemistry, one each from the Departments of Anatomy and Pathology, and three new faculty appointees in a new program in basic cancer research. We recognize that one of the most critical obstacles to a deeper understanding of malignant transformation is lack of incisive knowledge of the properties of cancer cell membranes. By pooling our talents and resources, we plan to mount a comprehensive program to explore many facets of cell surface properties that initiate and perpetuate malignancy; hopefully, this approach will point the way to more rational therapy. Although the research effort is completely integrated, it encompasses four major components: 1) structural organization and physicochemical properties of cancer cell membranes, RNA tumor virus membranes, and reconstituted cancer cell and virus membranes, to be studied by techniques such as fluorescence polarization, NMR spectroscopy, electron spin resonance spectroscopy and scanning calorimetry; 2) synthesis, characterization, location and functions of membrane proteins and glycoproteins of transformed cells and RNA tumor viruses as determined by peptide mapping, glycosylation, primary and secondary structure, surface labeling, phagocytic (inside-out) vesicles and cell-cell or virus-cell interactions; 3) comparative membrane and surface properties of transformed and untransformed cells studied in transformed temperature-sensitive mutants, particularly in relation to transport mechanisms, surface antigenic determinants, genetic regulation, energy metabolism and relationship to surface morphology as determined by scanning electron microscopy; and 4) lysosomal hydrolases in alteration of cell membrane surfaces and their role in invasive properties of malignant tumors. The research objectives of this program-project proposal do not overlap with any existing research grants.